Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China.
Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Nat Commun. 2017 May 25;8:15201. doi: 10.1038/ncomms15201.
A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and HO treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli.
许多 microRNAs（miRNAs，miRs）已被证明在骨骼肌萎缩中发挥作用，但它们的作用尚未完全阐明。在这里，我们显示 miR-29b 可促进细胞和小鼠模型中对不同萎缩刺激的骨骼肌萎缩。miR-29b 促进 C2C12 或原代成肌细胞分化的肌管萎缩，相反，其抑制可减弱地塞米松（Dex）、TNF-α 和 HO 处理诱导的萎缩。miR-29b 靶向 IGF-1 和 PI3K(p85α) 是诱导肌肉萎缩所必需的。在体内，miR-29b 的过表达足以促进肌肉萎缩，而 miR-29b 的抑制可减弱去神经和固定引起的萎缩。这些数据表明，miR-29b 通过靶向 IGF-1 和 PI3K(p85α) 促进多种类型的肌肉萎缩，而抑制 miR-29b 可能代表针对不同刺激引起的肌肉萎缩的治疗方法。
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